PPH protocol
The patients were managed medically and surgically according to the most
recent French guidelines 4,20,21. Antifibrinolytic
prophylaxis was given according to the investigators’ choice in both
groups. Administration of tranexamic acid (TXA) or fibrinogen within 48h
prior to inclusion was a non-inclusion criteria, but was allowed after
inclusion 19. After intravenous infusion of the
investigational medicinal product (IMP: 3 g fibrinogen concentrate or
placebo), the decision to transfuse blood or not was taken based on
European guidelines 22. Administration of fibrinogen
concentrate (Clottafact®, LFB, Les Ulis – France) beyond 60 minutes
after the start of the IMP and of other rescue procedures were allowed
as safety measures following strict rules to control bias19. The start time of the IMP infusion corresponded to
H0. Blood samples were taken at H0, H2, H6 and D2 (Figure S1). The
fibrinogen dose was set according to a preliminary kinetics study.